The project investigates mechanisms by which human airway epithelial cells respond to ionizing radiation, especially a-particles like those implicated in the development of lung cancer in individuals exposed to radon and radon daughter products. The research considers how responses to a-emitters may be modified by reactive oxygen species (ROS) and other conditions that likely occur in vivo along with radon and radon daughter exposure. Mechanisms that cause postexposure delays in G1 phase will be investigated because: 1) such delays may provide cells with additional time to repair damaged DNA before DNA replication, and 2) escape from the G1 checkpoint or limitation of the otherwise normal duration of the G1 checkpoint in response to a given level of DNA damage may limit the repair efficiency of damaged DNA before initiation of replication. Results from this project expectedly will provide an explanation about how genomic alterations caused by ionizing radiations may go unrepaired and become heritable. Moreover, our results concerning ROS will expand our understanding of the roles ROS may play in the development of lung cancer following exposure to particles. Because the project relies heavily on flow cytometric approaches for cell-cycle analyses concurrently with analyses of immunofluorescence-labeled proteins, we are further developing our multiparameter flow cytometer and associated approaches for these measurements. We are also exploring the use of phase-sensitive-detection flow cytometry for such measurements.